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1.
J Natl Compr Canc Netw ; 22(5): 290-298, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-39019054

RESUMO

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/terapia , Melanoma/diagnóstico , Melanoma/patologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Estadiamento de Neoplasias , Oncologia/normas , Oncologia/métodos
2.
Am J Dermatopathol ; 46(1): 21-30, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37982498

RESUMO

ABSTRACT: Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used to facilitate distinction of benign and malignant melanocytic proliferations. We hypothesized that evaluation of 1 institution's experience with PRAME labeling in a large number of consecutive cases might elucidate additional strengths and potential pitfalls and reveal base rates of positivity versus negativity in 1 academic practice. Pathology reports for all specimens on which PRAME labeling was performed at our institution between January 2021 and May 2022 were retrieved from our database. Eighty percent of conventional malignant melanomas were labeled diffusely positive with PRAME; there were no significant differences in mean age, sex, site, Breslow depth, ulceration status, or American Joint Committee on Cancer pathological tumor stage when comparing diffusely PRAME-positive malignant melanomas with those that lack diffuse labeling. Although no banal melanocytic nevi were labeled with PRAME, 13% of dysplastic nevi were diffusely PRAME positive, with junctional proliferations, severe atypia, male gender, and older age being associated with PRAME positivity. As some but not all ambiguous melanocytic lesions in which malignancy could not be excluded based on morphology alone were diffusely PRAME positive, PRAME's accuracy in predicting malignancy remains unclear to the authors; further study is needed to assess the precision to which PRAME immunohistochemistry can separate benign borderline lesions from their malignant counterparts. Among nonmelanocytic lesions, some poorly differentiated tumors, including atypical fibroxanthomas, can be PRAME positive. This series underscores the importance of clinicopathologic correlation and shows that diffuse PRAME positivity is highest in conventional malignant melanomas (∼80%, or 8 of 10 lesions), is seen in about half of challenging borderline lesions at our institution, and can be observed in lesions diagnosed as dysplastic nevi by our group (∼10% or 1 in 10 lesions), as well as in rare poorly differentiated malignancies.


Assuntos
Síndrome do Nevo Displásico , Melanoma , Neoplasias Cutâneas , Humanos , Masculino , Antígenos de Neoplasias , Diagnóstico Diferencial , Síndrome do Nevo Displásico/patologia , Imuno-Histoquímica , Melanócitos/patologia , Melanoma/diagnóstico , Melanoma/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Fatores de Transcrição , Feminino
3.
Proc Natl Acad Sci U S A ; 118(37)2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34504008

RESUMO

Chronic ultraviolet (UV) radiation exposure is the greatest risk factor for cutaneous squamous cell carcinoma (cSCC) development, and compromised immunity accelerates this risk. Having previously identified that epidermal Langerhans cells (LC) facilitate the expansion of UV-induced mutant keratinocytes (KC), we sought to more fully elucidate the immune pathways critical to cutaneous carcinogenesis and to identify potential targets of intervention. Herein, we reveal that chronic UV induces and LC enhance a local immune shift toward RORγt+ interleukin (IL)-22/IL-17A-producing cells that occurs in the presence or absence of T cells while identifying a distinct RORγt+ Sca-1+ CD103+ ICOS+ CD2+/- CCR6+ intracellular CD3+ cutaneous innate lymphoid cell type-3 (ILC3) population (uvILC3) that is associated with UV-induced mutant KC growth. We further show that mutant KC clone size is markedly reduced in the absence of RORγt+ lymphocytes or IL-22, both observed in association with expanding KC clones, and find that topical application of a RORγ/γt inhibitor during chronic UV exposure reduces local expression of IL-22 and IL-17A while markedly limiting mutant p53 KC clonal expansion. We implicate upstream Toll-like receptor signaling in driving this immune response to chronic UV exposure, as MyD88/Trif double-deficient mice also show substantially reduced p53 island number and size. These data elucidate key immune components of chronic UV-induced cutaneous carcinogenesis that might represent targets for skin cancer prevention.


Assuntos
Interleucinas/metabolismo , Queratinócitos/patologia , Linfócitos/patologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Neoplasias Cutâneas/patologia , Pele/patologia , Raios Ultravioleta/efeitos adversos , Animais , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinogênese/efeitos da radiação , Células Cultivadas , Imunidade Inata/imunologia , Interleucinas/genética , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Células de Langerhans/imunologia , Células de Langerhans/metabolismo , Células de Langerhans/patologia , Células de Langerhans/efeitos da radiação , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/efeitos da radiação , Camundongos , Mutação , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Pele/metabolismo , Pele/efeitos da radiação , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/metabolismo , Interleucina 22
4.
Ann Surg Oncol ; 29(1): 415-424, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34494169

RESUMO

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. Our report describes the evolution of management and characteristics associated with recurrence, disease-specific survival (DSS) and overall survival (OS) in the treatment of MCC. METHODS: A single institution retrospective review of MCC and SEER data to determine factors associated with RFS, DSS, and OS using a multivariable Cox regression on inverse-probability weighted cohorts. RESULTS: One hundred fifty-nine patients were identified with a median age of 75. Of these, 96% were Caucasian and 60% male. Fifty-eight out of 159 (36%) of all patients were deceased with 21/58 (36%) dead from MCC with a median follow-up of 3.1 years. Institutionally, trends over time demonstrated an increased use of immunotherapy with a concomitant decrease in chemotherapy and decreased use of radiotherapy alone. Institutionally and nationally, there has been increased surgical nodal staging. Institutionally, factors associated with shorter DSS included advanced age, active cigarette smoker (p = 0.002), cT2 disease (p = 0.007), and MCC with unknown primary (p < 0.001). Institutionally, factors associated with shorter OS included ages ≥ 75 years (p < 0.001), an immunocompromised state (p < 0.001), truncal primary site (p = 0.002), and cT2 disease (HR 9.59, p < 0.001). CONCLUSION: Changing practice patterns in MCC management have been driven by the adoption of immunotherapy. Our study highlights that competing risks of mortality in MCC patients likely prevents OS from being an accurate surrogate outcome measure to understand factors associated with DSS.


Assuntos
Carcinoma de Célula de Merkel , Radioterapia (Especialidade) , Neoplasias Cutâneas , Idoso , Carcinoma de Célula de Merkel/terapia , Feminino , Humanos , Imunoterapia , Masculino , Estudos Retrospectivos , Neoplasias Cutâneas/terapia
5.
N Engl J Med ; 379(26): 2540-2546, 2018 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-30586518

RESUMO

There is evidence that Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling plays a role in the pathogenesis of sarcoidosis. We treated a patient with cutaneous sarcoidosis with the JAK inhibitor tofacitinib; the patient had not previously had a response to medications and had not received systemic glucocorticoids. This treatment resulted in clinical and histologic remission of her skin disease. Sequencing of RNA and immunohistochemical examination of skin-lesion samples obtained from the patient before and during therapy and immunohistochemical testing of lesion samples obtained from other patients with cutaneous sarcoidosis support a role for JAK-STAT signaling in cutaneous sarcoidosis. (Funded by the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research and others.).


Assuntos
Janus Quinases/antagonistas & inibidores , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Sarcoidose/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Pele/patologia , Feminino , Humanos , Imuno-Histoquímica , Janus Quinases/metabolismo , Pessoa de Meia-Idade , Indução de Remissão , Fatores de Transcrição STAT/metabolismo , Sarcoidose/genética , Sarcoidose/patologia , Sarcoidose Pulmonar/tratamento farmacológico , Análise de Sequência de RNA , Transdução de Sinais , Pele/metabolismo , Dermatopatias/genética , Dermatopatias/patologia
6.
J Natl Compr Canc Netw ; 19(4): 364-376, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33845460

RESUMO

Over the past few years, the NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways for treatment of microscopic satellitosis (added in v2.2020), and the following Principles sections: Molecular Testing (added in v2.2019), Systemic Therapy Considerations (added in v2.2020), and Brain Metastases Management (added in v3.2020). The v1.2021 update included additional modifications of these sections and notable revisions to Principles of: Pathology, Surgical Margins for Wide Excision of Primary Melanoma, Sentinel Lymph Node Biopsy, Completion/Therapeutic Lymph Node Dissection, and Radiation Therapy. These NCCN Guidelines Insights discuss the important changes to pathology and surgery recommendations, as well as additions to systemic therapy options for patients with advanced disease.


Assuntos
Melanoma , Neoplasias Cutâneas , Neoplasias Encefálicas/secundário , Humanos , Excisão de Linfonodo , Melanoma/diagnóstico , Melanoma/cirurgia , Melanoma/terapia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/terapia
7.
J Natl Compr Canc Netw ; 18(2): 120-131, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32023525

RESUMO

The NCCN Guidelines for Uveal Melanoma include recommendations for staging, treatment, and follow-up of patients diagnosed with uveal melanoma of the choroid or ciliary body. In addition, because distinguishing between uveal melanoma and benign uveal nevi is in some cases difficult, these guidelines also contain recommendations for workup of patients with suspicious pigmented uveal lesions, to clarify the tests needed to distinguish between those who should have further workup and treatment for uveal melanoma versus those with uncertain diagnosis and low risk who should to be followed and later reevaluated. These NCCN Guidelines Insights describe recommendations for treatment of newly diagnosed nonmetastatic uveal melanoma in patients who have already undergone a complete workup.


Assuntos
Oncologia/normas , Melanoma/terapia , Recidiva Local de Neoplasia/prevenção & controle , Guias de Prática Clínica como Assunto , Neoplasias Uveais/terapia , Braquiterapia/normas , Educação Médica Continuada , Enucleação Ocular/normas , Humanos , Oncologia/educação , Oncologia/métodos , Melanoma/diagnóstico , Melanoma/patologia , Oncologistas/educação , Carga Tumoral , Neoplasias Uveais/diagnóstico , Neoplasias Uveais/patologia
8.
J Am Acad Dermatol ; 82(3): 612-621, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31185230

RESUMO

BACKGROUND: Sarcoidosis and granuloma annulare (GA) are cutaneous granulomatous disorders that can be difficult to treat. There is evidence of underlying Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway activation in sarcoidosis, suggesting that JAK inhibition might be effective. OBJECTIVE: To evaluate treatment with tofacitinib, a JAK inhibitor, in patients with recalcitrant sarcoidosis and GA. METHODS: A prospective evaluation of tofacitinib in 4 consecutive patients with recalcitrant cutaneous sarcoidosis (n = 3) and generalized GA (n = 1) was conducted. Immunohistochemical analysis of skin biopsy specimens from other patients with sarcoidosis (n = 21) and GA (n = 17) was performed to characterize patterns of JAK-STAT pathway activation. RESULTS: Tofacitinib resulted in a mean improvement in the baseline Cutaneous Sarcoidosis Activity and Morphology Instrument and Granuloma Annulare Scoring Index scores of 96% (standard deviation, 2%). Histologic resolution of disease was documented in all patients (3 out of 3) who had skin biopsies while receiving therapy. Constitutive STAT1 and STAT3 activation was observed in both sarcoidosis and GA, albeit in different patterns. Signal regulatory protein α may explain the differences in JAK-STAT signaling between sarcoidosis and GA. LIMITATIONS: The study is limited by the small number of participants. CONCLUSIONS: Tofacitinib resulted in dramatic improvement in 4 patients with cutaneous sarcoidosis and GA. Larger studies are underway to better understand this effect.


Assuntos
Granuloma Anular/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Indução de Remissão/métodos , Sarcoidose/tratamento farmacológico , Adulto , Idoso , Biópsia , Feminino , Granuloma Anular/diagnóstico , Granuloma Anular/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sarcoidose/diagnóstico , Sarcoidose/patologia , Índice de Gravidade de Doença , Pele/patologia , Resultado do Tratamento
9.
Yale J Biol Med ; 93(1): 69-80, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32226338

RESUMO

The relationship between skin color and skin cancer is well established: the less melanin in one's skin the greater the risk for developing skin cancer. This review is in two parts. First, we summarize the current understanding of the cutaneous pigmentary system and trace melanin from its synthesis in the pigment cell melanosomes through its transfer to keratinocytes. We also present new methods for reducing melanin content in hyper-pigmented areas of skin such as solar lentigenes, melasma, and post-inflammatory hyperpigmentation. Second, we present evidence that at least one mechanism for the development of metastatic melanoma and other solid tumors is fusion and hybridization of leucocytes such as macrophages with primary tumor cells. In this scenario, hybrid cells express both the chemotactic motility of the leucocyte and the de-regulated cell division of the tumor cell, causing the cells to migrate a deadly journey to lymph nodes, distant organs, and tissues.


Assuntos
Hiperpigmentação , Melaninas/metabolismo , Neoplasias Cutâneas , Pigmentação da Pele/fisiologia , Humanos , Hiperpigmentação/metabolismo , Hiperpigmentação/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/prevenção & controle
10.
J Natl Compr Canc Netw ; 17(4): 367-402, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30959471

RESUMO

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.


Assuntos
Oncologia , Melanoma , Neoplasias Cutâneas , Humanos , Oncologia/normas , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Melanoma Maligno Cutâneo
11.
J Cutan Pathol ; 45(7): 473-477, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29569269

RESUMO

BACKGROUND: Lyme disease (LD) is one of the most common tick-borne diseases caused by several Borrelia species of spirochetes. Ixodes scapularis is responsible for the transmission of LD in the northeastern United States. The rate of infection varies with the duration of tick attachment to the host; however, this information may be unknown. In skin biopsies, it is often difficult to identify spirochetes. Testing of ticks is not routinely performed. Treatment is established by clinical presentation. OBJECTIVE: To test paraffin-embedded I. scapularis ticks for Borrelia by different methods. MATERIALS/METHODS: We examined 20 paraffin-embedded ticks by silver stain, immunohistochemical (IHC) and direct immunofluorescent (DIF) methods and compared the percentage of positivity with DIF results from the Connecticut Agricultural Experiment Station. RESULTS: The results were similar by DIF, which proved to be the most sensitive method, followed by the silver stain and IHC. CONCLUSION: We found that the identification of spirochetes in paraffin-embedded ticks was less difficult than in tissue with a comparable turnaround time to that of a routine biopsy. Timely identification of Borrelia in ticks may influence the clinical management of the patients.


Assuntos
Borrelia , Ixodes/microbiologia , Coloração pela Prata , Animais , Connecticut , Feminino , Técnica Direta de Fluorescência para Anticorpo , Imuno-Histoquímica , Masculino , Inclusão em Parafina , Sensibilidade e Especificidade
12.
Eur J Immunol ; 46(11): 2650-2658, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27546296

RESUMO

Organ transplantation in older people is increasing, but how aging impacts B-cell responses to organ transplantation is still unknown. Here, we show that the depletion of B cells with anti-CD20 antibodies has disparate effects depending on recipient age. In young murine recipients, anti-CD20 treatment impaired the ability of immune modulation to extend skin allograft survival. In contrast, anti-CD20 treatment extended allograft survival in aged recipients treated with immune modulation. Although regulatory B-cell function and the numbers of marginal and follicular B cells were similar between age groups, a subpopulation of B cells, termed age-associated B cells (ABCs), accumulated upon aging. ABCs isolated from aged mice exhibited upregulation of CD73, CD80, CD106, and TLR2 and an increased capacity to augment T-cell alloimmunity compared to ABCs from young mice. Importantly, ABCs from aged, but not young, mice impaired the ability of immune modulation to enhance allograft survival after adoptive transfer into young transplant recipients. Our study indicates that ABCs impair the immune regulation of allografts. Thus, recipient age needs to be considered when proposing B-cell-depleting immune therapy.


Assuntos
Envelhecimento/imunologia , Aloenxertos/imunologia , Linfócitos B/imunologia , Linfócitos B/patologia , 5'-Nucleotidase/genética , Transferência Adotiva , Animais , Anticorpos Monoclonais/administração & dosagem , Antígeno B7-1/genética , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante de Pele , Receptor 2 Toll-Like/genética , Transplante Homólogo , Molécula 1 de Adesão de Célula Vascular/genética
13.
Dermatol Surg ; 43(3): 431-436, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28079637

RESUMO

BACKGROUND: Atypical fibroxanthoma (AFX) is a rare cutaneous spindled cell neoplasm. For both diagnostic and therapeutic purposes, it is important to distinguish AFX from other poorly differentiated tumors, including undifferentiated pleomorphic sarcoma (UPS). OBJECTIVE: The authors aimed to identify the clinical, histologic, and immunohistochemical expression of LN2, ezrin, and CD10 in AFX and UPS tumors. METHODS AND MATERIALS: The authors retrospectively examined the charts of patients with AFX and UPS treated with Mohs micrographic surgery (MMS) at 2 academic institutions. Patient demographics, tumor characteristics, and clinical course data were collected. Immunohistochemical stains were performed on primary and recurrent AFX and UPS tumors with monoclonal antibodies against the B-cell marker LN2 (CD74), CD10, and ezrin. RESULTS: In the series of 169 patients with AFX included in this study, local recurrence was rare at 3%. In contrast, the seven patients with UPS had an aggressive clinical course with 1 local recurrence and 2 distant metastases. Immunohistochemistry staining for ezrin, LN2, and CD10 were similar in AFX and UPS tumors. CONCLUSION: AFX can be treated with MMS with rare instances of recurrence. Undifferentiated pleomorphic sarcoma has a more aggressive clinical course with increased risk for recurrence and metastasis. Staining with ezrin, LN2, and CD10 did not differentiate AFX or UPS tumors.


Assuntos
Antígenos de Diferenciação de Linfócitos B/análise , Biomarcadores Tumorais/análise , Proteínas do Citoesqueleto/análise , Histiocitoma Fibroso Maligno/diagnóstico , Antígenos de Histocompatibilidade Classe II/análise , Neprilisina/análise , Sarcoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Seguimentos , Histiocitoma Fibroso Maligno/metabolismo , Histiocitoma Fibroso Maligno/mortalidade , Histiocitoma Fibroso Maligno/cirurgia , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia de Mohs , Valor Preditivo dos Testes , Estudos Retrospectivos , Sarcoma/metabolismo , Sarcoma/mortalidade , Sarcoma/cirurgia , Sensibilidade e Especificidade , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/cirurgia , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
15.
J Cutan Pathol ; 43(5): 418-21, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26956940

RESUMO

Goltz syndrome (focal dermal hypoplasia) is an X-linked dominant disorder that is classically associated with yellowish papules representing fat herniation (superficial adipocytes). We report a series of three cases, with clinicopathologic correlation of biopsies from Blaschkoid streaks. A range of histopathologic features, including some underreported findings (increased papillary dermal blood vessels, decreased thickness of the dermis, and adipocytes high in the dermis), are reproducible and can strongly point to the correct diagnosis of Goltz syndrome.


Assuntos
Adipócitos , Derme , Hipoplasia Dérmica Focal , Adipócitos/metabolismo , Adipócitos/patologia , Adulto , Criança , Derme/irrigação sanguínea , Derme/metabolismo , Derme/patologia , Feminino , Hipoplasia Dérmica Focal/metabolismo , Hipoplasia Dérmica Focal/patologia , Humanos , Masculino
16.
J Cutan Pathol ; 43(10): 821-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27246995

RESUMO

BACKGROUND: Histopathologic diagnostic features such as tumor thickness, ulceration, mitoses, microsatellitosis and nodal metastases are principal pathologic staging components of cutaneous melanomas. We chose to focus on evaluating the presence of multinucleated giant cells in microscopic sections as a putative novel prognosticating diagnostic feature of melanoma. METHODS: We assembled a retrospective cohort comprised of 562 cases of melanoma. We annotated each case for a multitude of known clinicopathologic variables to allow robust statistical evaluation of our cohort. RESULTS: Only 37 cases (6.6%) exhibited the multinucleated giant cells phenotype. Virtually all multinucleated giant cells were localized in the reticular dermis. Of interest, melanomas with multinucleated giant cells were roughly twice more likely to occur on head and neck sites (p = 0.04). Melanomas with multinucleated giant cells phenotype had both comparable melanoma recurrence (p = 0.12) and similar melanoma-specific mortality when compared with melanomas without multinucleated giant cells phenotype (p = 0.26). CONCLUSION: Despite prior anecdotal reports possibly linking multinucleated giant cells phenotype to more aggressive clinical course, we find that melanomas with multinucleated giant cells phenotype is not associated with shorter survival.


Assuntos
Células Gigantes/patologia , Neoplasias de Cabeça e Pescoço/patologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Dermatol Surg ; 42 Suppl 1: S18-23, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26035047

RESUMO

BACKGROUND: Solid organ transplant recipients (SOTRs) are 100 times more likely to develop cutaneous squamous cell carcinoma (SCC) with greater metastatic propensity compared with the general population, likely due to chronic immunosuppression and adverse drug effects on keratinocytes. Tumor-associated macrophages (TAMs) play critical roles in malignancies, either aiding in eradication of malignant cells or promoting tumor growth. OBJECTIVE: The authors examined whether TAM density and polarization states differ between SOTRs and nontransplant individuals. MATERIALS AND METHODS: The authors obtained normal skin, SCC in situ (SCCis), and SCC from SOTRs and nontransplant patients (N = 45) and stained with macrophage marker CD68, M1 marker CD40, and M2 marker arginase-1. RESULTS: The authors report a significantly higher density of TAMs in both SCCis and SCC. The intratumoral macrophage infiltration in SCCis from SOTR was significantly decreased compared with nontransplant patients. Tumor-associated macrophages in SCCis and SCC displayed both M1 and M2 polarization, and M2 activation levels were significantly lower in SCC from SOTR. CONCLUSION: Tumor-associated macrophages are present in early carcinogenesis and may play a critical role in the transition from SCCis to SCC, before invasion of the basement membrane by tumor cells. The intratumoral macrophage density in early stages of tumor development is significantly affected in SOTR.


Assuntos
Carcinoma de Células Escamosas/imunologia , Hospedeiro Imunocomprometido , Macrófagos/imunologia , Transplante de Órgãos , Neoplasias Cutâneas/imunologia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Arginase/análise , Antígenos CD40/análise , Carcinoma in Situ/imunologia , Carcinoma in Situ/patologia , Contagem de Células , Polaridade Celular , Feminino , Humanos , Ativação de Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade
20.
J Am Acad Dermatol ; 73(2): 181-90, quiz 191-2, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26183967

RESUMO

The incidence of melanoma has steadily increased over the past 3 decades, with melanoma in situ comprising a disproportionately high percentage of the rising incidence. Our understanding of melanoma in situ has been shaped by epidemiologic and clinical studies. Central to a review of melanoma in situ is a focus on its epidemiology, pathology, biologic behavior, treatment, and clinical outcome, which may differ significantly from that of malignant melanoma. Part I of this continuing medical education article reviews the epidemiology, risk factors, and clinical features of melanoma in situ; part II covers the histopathology, treatment options, and clinical management.


Assuntos
Carcinoma in Situ/epidemiologia , Detecção Precoce de Câncer/métodos , Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Carcinoma in Situ/patologia , Educação Médica Continuada , Feminino , Humanos , Masculino , Melanoma/patologia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prevalência , Neoplasias Cutâneas/patologia , Estados Unidos/epidemiologia , Melanoma Maligno Cutâneo
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